Table 6 Safety of anti-IL agents (anakinra, canakinumab, and rilonacept) in refractory patients with AOSD: data from retrospective observational studies, nationwide survey, and clinical trials
Study | Design | Study drug | Adverse event, no. of patients |
|---|---|---|---|
Injection site reactions (ISR) | |||
Naumann et al. [62] | RO | Anakinra | 2/8 (25%) |
Laskari et al. [63] | RO | Anakinra | 5/25 (20%) |
Gerfaud-Valentine et al. [68] | RO | Anakinra | “Some”/6 |
Cavalli et al. [70] | RO | Anakinra | 2/20 (10%) |
Colafrancesco et al. [76] | RO | Anakinra | 28/140 (20%) |
Giampietro et al. [66] | Nationwide survey | Anakinra | “Some”/28 |
Ortiz-Sanjuan et al. [71] | Nationwide survey | Anakinra | 6/41 (14.6%) |
Nordstrom et al. [18] | Clinical trial (RCT) | Anakinra | 8/12 (66.6%) |
Diffuse cutaneous reactions (rash/urticaria/eczema) | |||
Laskari et al. [63] | RO | Anakinra | 3/25 (12%) |
Quartuccio et al. [65] | RO | Anakinra | 3/10 (30%) |
Toz et al. (abstract) [75] | RO | Anakinra | 1/7 (14.2%) |
Colafrancesco et al. [76] | RO | Anakinra | 12/140 (8.5%) |
Lequerre et al. [60] | Nationwide survey | Anakinra | 2/15 (13.3%) |
Ortiz-Sanjuan et al. [71] | Nationwide survey | Anakinra | 2/41 (4.8%) |
Feist et al. [33] | Clinical trial (post hoc analysis) | Canakinumab | 13/31 (41.9%) |
Infections (mild and severe) | |||
Laskari et al. [63] | RO | Anakinra | 6/25 mild (24%); 1/25 severe (4%) |
Cavalli et al. [70] | RO | Anakinra | 2/20 mild (10%) |
Colafrancesco et al. [76] | RO | Anakinra | 4/140 mild (2.8%); 2/140 severe (1.4%) |
Lequerre et al. [60] | Nationwide survey | Anakinra | 4/15 mild (26.6%); 1/15 severe (6.6%) |
Ortiz-Sanjuan et al. [71] | Nationwide survey | Anakinra | 3/41 mild (7.3%); 2/41 severe (4.8%) |
Rossi-Semerano et al. [73] | Nationwide survey | Anakinra | 2/35 severe (5.7%) |
Henderson et al. [61] | Clinical trial (POL dose escalation) | Rilonacept | 2/5 severe (40%) |
Feist et al. [33] | Clinical trial (post hoc analysis) | Canakinumab | 21/31 mild (67.7%); 2/31 severe (6.4%) |
Other adverse events | |||
Quartuccio et al. [65] | RO | Anakinra | 2/10 (20%) (thrombocytopenia) |
Colafrancesco et al. [76] | RO | Anakinra | 2/140 (1.4%) (thrombocytopenia) 1/140 (0.7%) (leukopenia) 1/140 (0.7%) (lymphoproliferative disorders) |
Lequerre et al. [60] | Nationwide survey | Anakinra | 1/15 (6.6%) (Hip osteonecrosis) |
Ortiz-Sanjuan et al. [71] | Nationwide survey | Anakinra | 3/41 (7.3%) (leukopenia) 1/41 (2.4%) (myopathy) |
Feist et al. [33] | Clinical trial (post hoc analysis) | Canakinumab | 18/31 (58%) (GI disorders) 10/31 (32.2%) (respiratory) |
Macrophage activation syndrome | |||
Colafrancesco et al. [76] | RO | Anakinra | 6/140 (4.2%) |
Colafrancesco et al. [76] | RO | Canakinumab | 1/4 (25%) |
Rossi-Semerano et al. [73] | Nationwide survey | Anakinra | 1/35 (2.8%) |
Henderson et al. [61] | Clinical trial (POL dose escalation) | Rilonacept | 1/5 (20%) |
Feist et al. [33] | Clinical trial (post hoc analysis) | Canakinumab | 3/31 (9.6%) |